title: Carbonic anhydrase inhibitors. Phenols incorporating 2- or 3-pyridyl-ethenylcarbonyl and tertiary amine moieties strongly inhibit Saccharomyces cerevisiae β-carbonic anhydrase.
abstract: A series of phenols incorporating tertiary amine and trans-pyridylethenyl-carbonyl moieties were assayed as inhibitors of the β-carbonic anhydrase (CA, EC 4.2.1.1) from Saccharomyces cerevisiae, ScCA. One of these compounds was a low nanomolar ScCA inhibitor, whereas the remaining ones inhibited the enzyme with KIs in the range of 23.5-95.4 nM. The off-target human (h) isoforms hCA I and hCA II were much less inhibited by these phenols, with KIs in the range of 0.78-23.5 µM (hCA I) and 10.8-52.4 µM (hCA II). The model organism S. cerevisiae and this particular enzyme may be useful for detecting antifungals with a novel mechanism of action compared to the classical azole drugs to which significant drug resistance emerged.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Ataturk University , Erzurum , Turkey .
authors.forename: Sinan
authors.initials: S
authors.lastname: Bilginer
authors.forename: Elif
authors.initials: E
authors.lastname: Unluer
authors.forename: Halise Inci
authors.initials: HI
authors.lastname: Gul
authors.forename: Ebru
authors.initials: E
authors.lastname: Mete
authors.forename: Semra
authors.initials: S
authors.lastname: Isik
authors.forename: Daniela
authors.initials: D
authors.lastname: Vullo
authors.forename: Ozen
authors.initials: O
authors.lastname: Ozensoy-Guler
authors.forename: Serap
authors.initials: S
authors.lastname: Beyaztas
authors.forename: Clemente
authors.initials: C
authors.lastname: Capasso
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000595:Amino Acid Sequence; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D010802:Phylogeny; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000201:enzymology*; D016415:Sequence Alignment; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D010636:Phenols; D011725:Pyridines; D002256:Carbonic Anhydrases
keywords: Antifungalscarbonic anhydrase; Saccharomyces cerevisiae; phenols; pyridylethenyl-carbonyl